Assessment of The Effect of Apixaban in AF

Patients with an irregular heart rhythm called atrial fibrillation (AF) have an increased risk of forming blood clots inside the heart, that can then fragment and break off, travelling through the circulation to the brain, where it can cause blockage of the small blood vessels resulting in a stroke. Most patients with AF are prescribed blood thinning medications in an attempt to prevent such clot formation. The body has the ability through enzymes circulating in blood, to dissolve a clot once formed, such that even if a clot is formed, it is rapidly dissolved and no lasting damage is sustained. This is known as endogenous fibrinolysis. If this defence system is faulty or suboptimal, there is an increased risk of clot formation, resulting in stroke or heart attack. Currently, there are no available tablets to favourably modify this defence system of endogenous fibrinolysis. The investigators will assess how this defence system functions in patients with AF who are on different blood thinners. Then the investigators will also assess a group of patients before and during treatment with a relatively new blood thinner called apixaban, to assess the effect of this on the stickiness of blood and the ability of the blood to dissolve clots (endogenous fibrinolysis). All the blood thinners will be prescribed for clinical indications, not as part of the research. The research aspect of the study is that we will perform a blood test to assess endogenous fibrinolysis.

Understanding the effect of apixaban on endogenous fibrinolysis raises the possibility that apixaban, rather than other blood thinners, may be of particular use in patients with impaired fibrinolysis who are at particularly high risk of clots due to inefficient endogenous fibrinolysis.

Inclusion criteria

• Age >18 years
• Diagnosis of NVAF (nonvalvular atrial fibrillation)
• Requiring anticoagulation or antiplatelet therapy for thromboprophylaxis of stroke and systemic embolism
• No contra-indications to apixaban (except for those patients taking part in baseline cross-sectional study where this inclusion criterion does not apply)
• Patient does not meet any of the exclusion criteria below

Exclusion criteria

• Patient unwilling or unable to give informed consent
• Patient already taking antiplatelet or anticoagulant therapy (except for those patients taking part in baseline cross-sectional study, where this exclusion criterion does not apply)
• Patient who, in the opinion of the investigator, has significant hepatic or renal impairment likely to cause a bleeding diathesis
• Patient needing systemic high dose steroids or immunosuppression that may impact on platelet function
• Patient with ongoing active alcohol or substance abuse or demonstrates signs or clinical features of active substance abuse
• Patient with any major bleeding diathesis or blood dyscrasia at baseline (platelets<70 x 109/l, Hb<80 g/l, INR >1.4 (international normalized ratio), APTT (activated partial thromboplastin time ) > x 2UNL (upper normal limit) , leucocyte count< 3.5x 109/l, neutrophil count<1x 109/l).
• Patient currently involved in another investigational trial of a medicine or medical device